title: The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
abstract: BACKGROUND
  The Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine is given to >120 million infants each year worldwide. Most studies investigating the immune response to BCG have focused on adaptive immunity. However the importance of TCR-gamma/delta (γδ) T cells and NK cells in the mycobacterial-specific immune response is of increasing interest.
  
  
  METHODS
  Participants in four age-groups were BCG-immunized. Ten weeks later, in vitro BCG-stimulated blood was analyzed for NK and T cell markers, and intracellular IFNgamma (IFNγ) by flow cytometry. Total functional IFNγ response was calculated using integrated median fluorescence intensity (iMFI).
  
  
  RESULTS
  In infants and children, CD4 and CD4-CD8- (double-negative (DN)) T cells were the main IFNγ-expressing cells representing 43-56% and 27-37% of total CD3+ IFNγ+ T cells respectively. The iMFI was higher in DN T cells compared to CD4 T cells in all age groups, with the greatest differences seen in infants immunized at birth (p=0.002) or 2 months of age (p<0.0001). When NK cells were included in the analysis, they accounted for the majority of total IFNγ-expressing cells and, together with DN Vδ2 γδ T cells, had the highest iMFI in infants immunized at birth or 2 months of age.
  
  
  CONCLUSIONS
  In addition to CD4 T cells, NK cells and DN T cells, including Vδ2 γδ T cells, are the key populations producing IFNγ in response to BCG immunization in infants and children. This suggests that innate immunity and unconventional T cells play a greater role in the mycobacterial immune response than previously recognized and should be considered in the design and assessment of novel tuberculosis vaccines.
authors.affiliation: Murdoch Children's Research Institute, Parkville, Australia.
authors.forename: Christel
authors.initials: C
authors.lastname: Zufferey
authors.forename: Susie
authors.initials: S
authors.lastname: Germano
authors.forename: Binita
authors.initials: B
authors.lastname: Dutta
authors.forename: Nicole
authors.initials: N
authors.lastname: Ritz
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007223:Infant; D007371:Interferon-gamma / Q000097:blood*; D007694:Killer Cells, Natural / Q000145:classification / Q000166:cytology / Q000276:immunology*; D008297:Male; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D007371:Interferon-gamma